This is part 3 of the Renal & Urology News series on hyperphosphatemia in CKD patients.

Reducing serum phosphorus via dietary protein restriction may incur risks outweighing its benefits

Hyperphosphatemia is a known risk factor for death in both the general and CKD populations and a correlate of faster CKD progression (Clin J Am Soc Neph. 2006;1:825-831).

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Moreover, hyperphosphatemia results in additional mineral and bone disorders (MBDs), such as the inhibition of 1a-hydroxylation of 25-hydroxycalciferol via the hyperphosphatemia-induced fibroblast growth factor-23 (FGF-23) pathway. Both hyperphosphatemia and calcitriol deficiency may result in hyperparathyroidism and renal osteodystrophy (Semin Dial. 2005;18:290-295).

Hyperphosphatemia may also contribute to worsening vascular calcification and increased risk of cardiovascular morbidity. Hence, correction and prevention of hyperphosphatemia are main components of the management of CKD patients. 

A traditional approach to correcting serum phosphorus levels is to impose dietary protein restriction, as foods high in protein are primary sources of dietary phosphorus.

However, a reduction in dietary protein intake can lead to malnutrition and protein-energy wasting (PEW), both of which are strong risk factors for increased risk of death in dialysis patients (Am J Kidney Dis. 2006;48:37-49 and Semin Nephrol. 2009;29:3-14). PEW is usu-ally associated with chronic inflammation, sarcopenia, hypoalbuminemia, and weight loss.

Until recently, there were no data assessing the risks and benefits of dietary protein restriction in CKD patients. A recent study by Shinaberger et al (Am J Clin Nutr. 2008;88:1511-1518) addresses this important question.

Dr. Shinaberger and his collaborators hypothesized that a decline in serum phosphorus with a concomitant decline in protein intake increases the risk of death, whereas controlling serum phosphorus without restricting dietary protein intake is associated with improved survival in established maintenance hemodialysis (HD) patients. 

For the first six months of the three-year (2001-2004) cohort study, researchers examined changes in serum phosphorus and normalized protein catabolic rate (nPCR or nPNA), a surrogate of dietary protein intake. The subsequent mortality of the 30,075 prevalent HD patients involved was then assessed.

Four groups of HD patients were defined based on the direction of changes in serum phosphorus and nPCR. Compared with HD patients whose serum phosphorus and nPCR both rose over six months, those whose serum phosphorus decreased but nPCR increased had the greatest survival with a case-mix adjusted death risk ratio of 0.90, whereas those whose phosphorus increased but nPCR decreased or those whose phosphorus and nPCR both decreased had worse mortality, with death risk ratios of 1.11 and 1.06, respectively.

Hence, this study showed, for the first time, that the risk of controlling serum phosphorus by restricting dietary protein intake may outweigh its benefit and lead to increased mortality. MBD (Int Urol Nephrol. 2008;40:427-440) and PEW (Kidney Int. 2008;73:391-398) are common in patients with CKD.